The RSV F glycoprotein is a key target for vaccine-induced neutralizing antibody. Our hypothesis is that understanding the mechanism of antibody neutralization will be facilitated by defining the structure of F and the structure of epitopes associated with neutralization. This will allow novel antigen design. Characterizing the chemistry and post-translational modifications in F will also promote improved vaccine antigen design. We have advanced our stabilized prefusion F protein into clinical evaluation in a Phase 1 clinical trial, VRC 317. In this trial, we are evaluating safety, tolerability, and immunogenicity of our stabilized prefusion F protein (DS-Cav1) with or with alum adjuvant in healthy adults. In addition to neutralizing antibodies, the induction of both protective, disease-sparing CD8+ T cell responses are desirable in a vaccine candidate. These studies include evaluation of gene and vector-based vaccines expressing either the stabilized Pre-F protein or the wildtype F protein to vaccination with soluble Pre-F protein. We are also working with collaborators to assess immunogenicity of other vectors expressing our stabilized Pre-F protein.